The effect size of an analgesic investigation is influenced by three factors: (1) the inherent efficacy of the study medication, (2) study conduct, and (3) study design. A key study design component is the choice of primary endpoint. The purpose of this retrospective review was to compare the assay sensitivity of pain intensity endpoints (SPID) to pain relief endpoints (TOTPAR). This was accomplished by performing a systematic review of the literature using PubMed, summary basis of approvals, the Cochrane library and manual searches to identify acute pain studies that calculated both SPIDs and TOTPARs. Studies were included in this review if: (1) they were randomized, double-blind placebo controlled investigations involving study medication for post-surgical acute pain, (2) enough data was provided to calculate both a pain intensity and pain relief effect size for a single time point, and (3) the data was provided for a single dose time interval (e.g., single-dose studies or multiple-dose studies where data were captured for the first dose). A determination was made as to whether a greater effect size was demonstrated utilizing SPID or TOTPAR for a single time point within each study. Of the 10 studies examined, 8 studies showed greater effect sizes using TOTPAR as the efficacy outcome compared to its corresponding SPID. The magnitude of the differences between the two outcomes ranged from 4-40%. Conversely, 2 studies revealed SPID to produce a greater effect size. This review comparing effect sizes from multiple randomized studies suggests that TOTPAR may have better assay sensitivity than SPID. Although a more exhaustive literature search may lead to a definitive conclusion, our data underscores the importance of choosing the proper primary endpoint in the design and planning of clinical trials.
© 2013 Published by Elsevier Inc.